In this application we are requesting funds to continue our COBRE Center for Cancer Experimental Therapeutics (CCET) for five more years. Our center was among the first group of COBRE grants awarded in 2000. The mission of the CCET is to increase cancer-related research and NIH funding in the State of Kansas. It has been a very successful program (http://ccet.cobre.ku.edu/index.php). During the first ten years of the program our center has funded 26 full Project Awards and 27 smaller First Awards. Thirty tenure track assistant professors have received funding. Of these, 11 have been promoted with tenure and 12 are still on the tenure track. The CCET investigators have obtained 42 NIH-funded grants (17 R01s) and 37 grants from other agencies, leading to a total of about $36,500,000 in new funding to Kansas. These investigators have published 218 journal and book manuscripts on research supported by the CCET. An essential part of our COBRE program was the establishment of two research cores, a High Throughput Screening (HTS) Core and a Medicinal Chemistry (MDC) Core. The COBRE Cores are located in the Structural Biology Center (SBC) located on the University of Kansas West Campus. The modern 4,500 sq.ft. High Throughput Screening Core research/office complex is fully equipped with state-of-the-art instrumentation and the personnel have extensive experience in executing cell-based, biochemical, label-free, siRNA as well as high content screening campaigns. The primary goal of the HTS Core has been to make modern drug discovery tools available to biomedical researchers in the Greater Kansas City area, Kansas and beyond. The equally modern Medicinal Chemistry Core is housed in a laboratory of approximately 2000 square feet. The MDC Core works in conjunction with the HTS Core and in collaboration with COBRE investigators and other researchers. The tasks of the MDC Core are (1) to perform synthesis of known compounds necessary for biochemical studies, (2) to design and synthesize novel drug compounds as probes for ongoing studies, (3) to work with the HTS Core and its biology collaborators in carrying out optimization of hits obtained in screening campaigns, and (4) to synthesize fluorescent or affinity tagged analogs of existing probes when necessary for cell localization or target identification studies. In this Phase III application we are requesting funds to continue these successful research cores and to make them self-sustaining by the end of the five-year funding. In addition, we seek funding to support a Pilot Project program to help basic cancer research investigators obtain preliminary data to strengthen their applications to agencies for major funding. We plan to fund four projects per year. Finally, we request support for an Administrative Core to oversee the entire program, including the Pilot Project program and the two research cores.